Performance of fine motor skills is challenging for aging veterans with vision loss. Eye-hand coordination and integration of sensory input is essential to perform fine motor skills. Aging leads to reduced sensory input and is often accompanied by impaired vision and movement control. Efficient rehabilitation strategies for aging veterans with vision loss are lacking and need to be developed to enhance the adaptive capacity of the nervous system (plasticity) during motor learning. The long-term objectives of the proposed project are to help develop creative rehabilitative interventions and assistive technologies for aging veterans with vision loss. However, it is first necessary to identify effective interventions that would lead to enhancing neural plasticity during fine motor skill learning in healthy young adults. Neural plasticity in the motor cortex is strongly enhanced by the activation of excitatory N-methyl-D-aspartate (NMDA) pathways and inhibited by the activation of inhibitory gamma-aminobutyric acid (GABA). Although modulations of NMDAergic and GABAergic functions have been suggested in pharmacological studies, it is unknown whether physiologically secreted monoamines modulate these functions with heightened sympathetic nerve activity. We have recently found that physiologically heightened sympathetic nerve activity modulates neural activity for fine performance of precision tasks with a hand muscle. In particular, our preliminary observations suggested that physiologically heightened sympathetic nerve activity could enhance motor cortex intracortical facilitation (mediated by NMDA) and reduce motor cortex intracortical inhibition (mediated by GABA). Specific Aim: To examine the effects of physiologically heightened sympathetic nerve activity on motor cortex intracortical inhibition and facilitation when a hand muscle is relaxed and performing a precision task. Hypothesis: Motor cortex intracortical inhibition is disinhibited and intracortical facilitation is enhanced with physiologically heightened sympathetic nerve activity due to inhibited GABAergic functions and enhanced NMDAergic functions (The hypothesis is supported by our preliminary data. See Section 3-4). The identification of physiologic predictors for an intervention can help to target those individuals who best benefit from the intervention. This could lead to the development of new rehabilitative strategies based on the interactions between the sympathetic nervous system and the neuromuscular system PUBLIC HEALTH RELEVANCE: The mission of the Atlanta VA Rehabilitation R&D Center is to improve the function, independence, and quality of life of aging veterans. Research is directed towards understanding the mechanisms underlying impairments and disabilities, and applying this to the design, testing, and evaluation of creative rehabilitative interventions. The hand's fine motor skills and visual acuity are degraded with age, and this is related to greater motor output variability of the index finger in older adults. To develop effective interventions, it is imperative to understand the basic neuro-physiological mechanisms underlying this increased motor output variability in older adults.The objective of the proposed study is to try and understand whether heightened sympathetic nerve activity influences cortical excitability and motor output variability in healthy young adults. We also would like to understand if these effects are exacerbated with the absence of visual feedback.